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Title: Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke
Authors: Pitchaya Matchimakul
Gabriel Rinaldi
Sutas Suttiprapa
Victoria H. Mann
Anastas Popratiloff
Thewarach Laha
Rafael N. Pimenta
Christina J. Cochran
Sasithorn Kaewkes
Banchob Sripa
Paul J. Brindley
Khon Kaen University
George Washington University
Wellcome Trust Sanger Institute
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 10-Jun-2015
Citation: International Journal of Biochemistry and Cell Biology. Vol.65, (2015), 72-80
Abstract: © 2015 Elsevier Ltd. All rights reserved. Chronic infection with the food-borne liver fluke, Opisthorchis viverrini, frequently induces cancer of the bile ducts, cholangiocarcinoma. Opisthorchiasis is endemic in Thailand, Lao PDR, Cambodia and Vietnam, where eating undercooked freshwater fish carrying the juvenile stage of this pathogen leads to human infection. Because inhibition of apoptosis facilitates carcinogenesis, this study investigated modulation by thioredoxin from O. viverrini of apoptosis of bile duct epithelial cells, cholangiocytes. Cells of a cholangiocyte line were incubated with the parasite enzyme after which they were exposed hydrogen peroxide. Oxidative stress-induced apoptosis was monitored using flow cytometry, growth in real time and imaging of living cells using laser confocal microscopy. Immunolocalization revealed liver fluke thioredoxin within cholangiocytes. Cells exposed to thioredoxin downregulated apoptotic genes in the mitogen activated protein kinases pathway and upregulated anti-apoptosis-related genes including apoptosis signaling kinase 1, caspase 9, caspase 8, caspase 3, survivin and others. Western blots of immunoprecipitates of cell lysates revealed binding of thioredoxin to apoptosis signaling kinase 1. Together the findings indicated that thioredoxin from O. viverrini inhibited oxidative stress-induced apoptosis of bile duct epithelial cells, which supports a role for this liver fluke oxidoreductase in opisthorchiasis-induced cholangiocarcinogenesis.
ISSN: 18785875
Appears in Collections:Scopus 2011-2015

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